This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Atherosclerosis is a progressive disease that is characterized by the accumulation of lipids, monocytes, fibrous constituents, and various other inflammatory cells in the arterial wall. These deposits form vascular lesions known as atheromatous plaques, which contain necrotic cores and are separated from the arterial intima by a fibrous cap made up of collagen and smooth muscle cells. When these plaques become vulnerable to rupture, they release the inflammatory elements of the necrotic core into the artery, causing thrombosis and obstruction of arterial blood flow. This study analyzes the progression of atherosclerosis in ApoE-deficient, LDLR KO mice. Specifically, we hope to observe two-photon excited fluorescence (TPEF) signals from elastin fibers of the arterial wall and second-harmonic generation (SHG) signals from collagen in the fibrous caps of the vulnerable plaque regions. We also hope to see various cellular structures (e.g. macrophages, smooth muscle cells) and inflammatory elements (e.g. lipids) within the vascular wall, and perhaps identify varying degrees of vascular calcification.